The Risk of Systemic Diseases in Those with Psoriasis and Psoriatic Arthritis: from Mechanisms to Clinic
Total Page:16
File Type:pdf, Size:1020Kb
International Journal of Molecular Sciences Review The Risk of Systemic Diseases in Those with Psoriasis and Psoriatic Arthritis: From Mechanisms to Clinic Yu Ri Woo 1 , Chul Jong Park 2 , Hoon Kang 3 and Jung Eun Kim 3,* 1 Department of Dermatology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea; [email protected] 2 Department of Dermatology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Gyeonggi-do 14647, Korea; [email protected] 3 Department of Dermatology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-2-2030-2845; Fax: +82-2-2030-2849 Received: 11 August 2020; Accepted: 21 September 2020; Published: 24 September 2020 Abstract: Psoriasis and psoriatic arthritis (PsA) have been recently considered as chronic systemic inflammatory disorders. Over the past decades, enormous evidence indicates that patients with psoriasis and PsA have a higher risk of developing various comorbidities including cardiovascular disease, metabolic disease, cancers, infections, autoimmune disease, and psychiatric diseases. However, reported risks of some comorbidities in those with psoriasis and PsA are somewhat different according to the research design. Moreover, pathomechanisms underlying comorbidities of those with psoriasis and PsA remain poorly elucidated. The purpose of this review is to provide the most updated comprehensive view of the risk of systemic comorbidities in those with psoriasis and PsA. Molecular mechanisms associated with the development of various comorbidities in those with psoriasis and PsA are also reviewed based on recent laboratory and clinical investigations. Identifying the risk of systemic comorbidities and its associated pathomechanisms in those with psoriasis and PsA could provide a sufficient basis to use a multi-disciplinary approach for treating patients with psoriasis and PsA. Keywords: psoriasis; comorbidity; cardiovascular disease; psoriatic arthritis; infection; cancer; sleep disorder; metabolic syndrome; autoimmune disease 1. Introduction Psoriasis is a common chronic immune-mediated inflammatory cutaneous disorder that affects about 0.91%–8.5% of the population [1]. Cutaneous manifestation of psoriasis can be characterized by well-demarcated erythematous thick scaly papules and plaques at distinct sites or disseminated over the whole skin. Such distinctive skin manifestations of psoriasis are due to disrupted differentiation and proliferation of keratinocytes resulting from interaction between altered immune cells and keratinocytes in a genetically-susceptible patient [2]. Besides the skin, similar inflammatory reactions can also occur at joints of susceptible patients and cause psoriatic arthritis (PsA), a form of arthritis. The diverse inflammatory molecules are released in skin lesions and joints of patients with psoriasis and PsA, and the vast majority of these molecules are also released into systemic circulation [3]. Indeed, the inflammation in those with psoriasis and PsA not only affects their skin and joints, but also spreads into their systemic circulation [3]. These findings provide a pathogenic basis for a possible association of various comorbidities with psoriasis and PsA. In 1897, Strauss et al. [4] first reported the association between psoriasis and diabetes mellitus. Thereafter, various epidemiological studies have reported the association between psoriasis and Int. J. Mol. Sci. 2020, 21, 7041; doi:10.3390/ijms21197041 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2020, 21, 7041 2 of 28 possible comorbid diseases, including venous vascular disease such as thrombophlebitis, and venous thromboembolism and arterial vascular disease such as myocardial infarction, angina, and stroke [5–8]. Due to extensive methodological progress, many epidemiological studies have reported that the prevalence of various comorbidities is increased in those with psoriasis and PsA. Diverse disorders and their associated risk factors have also been identified. However, there remains an inconsistency among reported results regarding the risk of comorbidities in those with psoriasis and PsA. Therefore, the aim of this study was to review the most up-to-date epidemiological data to identify the possible risk of various comorbid diseases in those with psoriasis and PsA. Among diverse comorbidities of those with psoriasis and PsA, this study focused on the risk of cardiovascular disease, metabolic syndrome, cancer, infection, autoimmune disorders, and psychiatric diseases in those with psoriasis and PsA in a more detailed manner. Moreover, this study intended to further analyze possible etiopathogenetic mechanisms of psoriasis and PsA and their comorbid disorders. Identifying the factual burden of comorbid disease in those with psoriasis and PsA might help us comprehensively manage patients with psoriasis and PsA. 2. The Risk of Cardiovascular Disease and Metabolic Syndrome in Psoriasis and Psoriatic Arthritis Various studies have reported the association between cardiovascular disease (CVD) and psoriasis. In 2006, Gelfand et al. [9] performed a large population-based cohort study and found that severe psoriasis was an independent risk factor of myocardial infarction (MI). Using prospective data from the United Kingdom General Practice Research Database, they found that the incidence of MI per 1000 person-years was 3.58 (95% confidence interval (CI), 3.52–3.65) for healthy controls, 4.04 (95% CI, 3.88–4.21) for patients with mild psoriasis, and 5.13 (95% CI, 4.22–6.17) for patients with severe psoriasis [9]. They also revealed that the adjusted relative risk (RR) for MI was 1.25 (95% CI: 1.14–1.46) for 30-year-old patients with mild psoriasis and 3.10 (95% CI: 1.98–4.86) for 30-year-old patients with severe psoriasis. The adjusted RR for MI was 1.08 (95% CI: 1.03–1.16) for 60-year-old patients with mild psoriasis and 1.36 (95% CI: 1.13–1.64) for 60-year-old patients with severe psoriasis. These results imply that younger patients with severe psoriasis have a higher risk of MI than older patients. This study instigated various researchers to further identify the risk of CVD in psoriasis. Consequently, various epidemiological studies have reported that psoriasis is an independent risk factor for major adverse cardiovascular events (MACEs) including MI, stroke, and death caused by CVD. Although some studies have not found a statistically significant association between psoriasis and MACE [10–13], the majority of systematic review and meta-analysis have consistently shown significant associations between diverse CVDs and psoriasis [14–21]. Results from systematic reviews and meta-analyses assessing the association between CVD and psoriasis are summarized in Table1. Among them, Samarasekera et al. [18] and Armstrong et al. [19] both stratified the risk of CVD considering the severity of psoriasis and observed a higher risk of CV mortality, MI, and stroke in psoriasis patients with more severe disease. Concerning disease duration, Egeberg et al. [22] found that a longer disease duration had a stronger association with the risk of MACE (OR: 1.01; 95% CI: 1.00–1.01) than a shorter disease duration. Int. J. Mol. Sci. 2020, 21, 7041 3 of 28 Table 1. Summary of results from systematic reviews and meta-analyses evaluating the risk of cardiovascular disease in patients with psoriasis and psoriatic arthritis. Identified Risk Among Study Number Study Population The Relative Risk of Measures CV Conditions Psoriasis CVD in total OR 1.4 (1.2–1.7) CVD, IHD, Psoriasis patients: 503,686 IHD OR 1.5 (1.2–1.9) 1 [14] cerebrovascular Controls: 29,686,694 Cerebrovascular disease OR 1.1 (0.9–1.3) disease, and CV mortality CV mortality OR 0.9 (0.4–2.2) Stroke RR 1.26 (1.12–1.41) Psoriasis patients + controls: Stroke, MI, CVD, and MI RR 1.32 (1.13–1.55) 2 [15] 6,230,774 CV mortality CVD RR 1.47 (1.30–1.60) CV mortality RR 1.33 (1.00–1.77) Cohort studies: MI OR 1.25 (1.03–1.52), CAD OR 1.20 (1.13–1.27), Psoriasis patients: 324,650 stroke OR 1.02 (0.92–1.14) 3 [16] MI, CAD, and stroke Controls: 5,309,087 Cross-sectional studies: MI OR 1.57 (1.08–2.27), CAD OR 1.84 (1.09 –3.09), stroke OR 1.14 (1.08–1.19) CV events: MI, IHD, cerebral Psoriasis patients: 367,358 4 [17] ischemic stroke, and sudden CV events OR 1.28 (1.18–1.38) Controls: 9,199,656 cardiac death All psoriasis: MI HR 1.40 (1.03–1.89) and stroke HR 1.13 (1.01–1.26) Psoriasis patients: 488,315 Mild psoriasis: CVD mortality SMR 1.03 (0.86–1.25), MI HR 1.34 (1.07– 1.68), and stroke (mild: 327,418; severe: CVD mortality, MI, and 5 [18] HR 1.15 (0.98–1.35) 12,854) Stroke Severe psoriasis: CVD mortality SMR 1.37 (1.17–1.60), CVD mortality Controls: 10,024,815 HR 1.57 (1.26–1.96), MI HR 3.04 (0.65–14.35) and stroke HR 1.59 (1.34–1.89) Psoriasis patients: 218,654 Mild Psoriasis: MI RR 1.29 (1.02–1.63), stroke RR 1.12 (1.08–1.16) (mild: 201,239; severe: MACE: CV mortality, 6 [19] Severe Psoriasis: MI RR 1.70 (1.32–2.18), stroke RR 1.56 (1.32–1.84), 17,415) MI, and stroke CV mortality RR 1.39 (1.11–1.74) Controls: 9,914,799 Psoriasis patients: 1,862,297 Overall CV RR 1.24 (1.18–1.31), MI RR 1.24 (1.11–1.39) 7 [20] MI, CVD, and CV death Controls: 43,407,300 Vascular disease RR 1.27 (1.12–1.43), CV Mortality RR 1.41 (0.97–2.04) MI and stroke RR 1.20 (1.10–1.31) Psoriasis patients: 326,598 8 [21] MI, and stroke MI RR 1.22 (1.05–1.42) Controls: 5,230,048 Stroke RR 1.21 (1.04–1.40) Psoriatic arthritis CVD OR 1.43 (1.24–1.66) CVD, CV events Psoriatic arthritis patients: CV events 1.55 (1.22–1.96) Morbidity risks for MI, 1 [23] 32,973 Morbidity risk for MI OR 1.68 (1.31–2.15) cerebrovascular events, Controls: 4,568,723 Morbidity risk for cerebrovascular events OR 1.22 (1.05–1.41) and heart failure Morbidity risk for heart failure OR 1.32 (1.11–1.57) Abbreviations: CAD, coronary artery disease; CV, cardiovascular; HR, hazard ratio; IHD, ischemic heart disease; MACE, major adverse cardiovascular events; MI, myocardial infarction; OR, odds ratio; RR, relative risk; SMR, standardized mortality ratio.